The proposed research seeks to identify specific neurobiologic actions in animals of acute and chronic exposure to and withdrawal from Li levels which stabilize affective psychoses in humans. Using electrophysiologic methods of extracellular unit recording, microiontophoretic administration, and electrical stimulation of selected synaptic pathways to identifiable target cells, Li will be investigated for selective actions on specific modes and sites of chemical synaptic transmission. With identification of significant Li effects, intracellular recordings and pharmacological perturbations will be used to determine the mechanism. Selected populations of cells known now or to be characterized as targets of combinations of noradrenergic, dopaminergic, serotonergic or cholinergic inputs will be used to evaluate selectivity of Li actions on the effectiveness of the pathways and on the responses of target cells to iontophoretic administration of the transmitter. This combination of evaluative methods will discriminate between pre-synaptic and post-synaptic effects of Li. Transmission specific effects will be evaluated quantitatively in rats treated with Li for short-terms (iontophoretic administration or single parenteral injections) and for long terms (twice daily injections for 3 weeks or longer to maintain plasma levels at 1.5-2.0 meq/L). In long terms Li-treated rats, biochemical and histochemical assessment will be performed to evaluate physiologic changes. Amino acid mediated synaptic and neuronal responses will be evaluated for possible non-monoaminergic Li actions. These experimental results can provide a definitive characterization of the sites, mechanisms, and functional consequences of Li action in terms of specific sensitive neuronal pathways. By providing insight into the fundamental neuronal processes by which Li treats affective diseases, these studies may help to pursue the psychopathologic defects of these psychoses.